Terpene-Enriched Nitazoxanide-Loaded Chondrosomes: Aerodynamic Characterization and In Silico Evaluation of Antiviral Activity

Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. Using a D-optimal design, the effects of factors on entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) were determined, and the optimal formulation was selected. Results: The optimum TEC exhibited an EE% of 98.87 ± 0.69, a PS of 129.43 ± 5.43 nm, a polydispersity index (PDI) of 0.433 ± 0.022, and a ZP of −25.99 ± 0.99 mV. The optimum TEC was lyophilized to attain a dry powder. Further, the differential scanning calorimetry test confirmed that NIT was transformed from crystalline to amorphous form inside the optimum TEC. In addition, the mucoadhesion test confirmed the ability of the optimum TECs to adhere to pulmonary tissues. Additionally, NIT binding to the active site of SARS-CoV-2 enzymes was investigated using in silico analysis. When compared to NIT, the aerodynamic characteristics of the lyophilized optimum TECs employing the cascade impactor showed superior residence in the lungs. Conclusions: These findings suggest that loading NIT into TECs enhanced its antiviral activity, as indicated by the in vitro cytotoxicity study. Overall, the results point to NIT-loaded TECs as a potentially effective pulmonary delivery system for COVID-19 treatment.